Summary
The clinical picture and drug metabolism in 36 consecutive patients with alpha-methyldopa — induced hepatic injury were investigated. The diagnosis was based on case history and biochemical, histological and follow-up studies after withdrawal the drug. Alpha-methyldopa-induced liver damage was found to occur in two phases, acutely within months and chronically within years after beginning treatment. Differences were also found in clinical symptoms and the results of liver tests on the patients if they were divided on the basis of the time factor. Drug metabolism was impaired in patients with alpha-methyldopa-induced liver damage, as indicated by low cytochrome P-450 level in liver biopsies and prolonged antipyrine elimination rate from plasma. Disappearance of the symptoms and normalisation of the liver tests after drug withdrawal occurred faster in patients with an acute type of hepatotoxicity than in subjects with delayed onset of the symptoms. The occurrence of hepatotoxicity in four members of a family suggests a genetic disposition to alpha-methyldopa-induced hepatic injury. The occurrence of two phases of liver damage suggests that a possible mechanism for acute hepatotoxicity might be an allergic reaction to metabolic intermediates produced during breakdown of alpha-methyldopa in the liver. For cases of delayed onset the cause might be increasing damage to microsomal liver protein due to covalent binding during long-term exposure to the drug.
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Sotaniemi, E.A., Hokkanen, O.T., Ahokas, J.T. et al. Hepatic injury and drug metabolism in patients with alpha-methyldopa-induced liver damage. Eur J Clin Pharmacol 12, 429–435 (1977). https://doi.org/10.1007/BF00561062
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DOI: https://doi.org/10.1007/BF00561062